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Genetic support for the role of the NLRP 3 inflammasome in psoriasis susceptibility
Author(s) -
Carlström Maria,
Ekman AnnaKarin,
Petersson Stina,
Söderkvist Peter,
Enerbäck Charlotta
Publication year - 2012
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12049
Subject(s) - inflammasome , single nucleotide polymorphism , psoriasis , transmission disequilibrium test , genotype , immunology , snp , aim2 , allele , pathogenesis , medicine , pyrin domain , genetics , biology , gene , inflammation
Abstract NACHT leucine‐rich repeat‐ and PYD ‐containing ( NLRP )3 protein controls the inflammasome by regulating caspase‐1 activity and interleukin ( IL )‐1β processing. The contribution of IL ‐1β in the pathogenesis of psoriasis is well recognized. Polymorphisms in NLRP 3 and caspase recruitment domain–containing protein ( CARD )8, a negative regulator of caspase‐1 activity, have been associated with susceptibility to common inflammatory diseases, such as Crohn's disease and rheumatoid arthritis. To investigate the role for genetic variants in the NLRP 3 inflammasome in psoriasis susceptibility. In a patient sample comprising 1988 individuals from 491 families and 1002 healthy controls, genotypes for four selected single‐nucleotide polymorphisms ( SNP s) in NLRP 3 (three SNP s) and CARD 8 (one SNP ) were determined by T aq M an ® Allelic Discrimination. Using the transmission disequilibrium test ( TDT ), a significant increase in the transmission of the NLRP 3 rs10733113G genotype to a subgroup of patients with more widespread psoriasis was demonstrated ( P = 0.015). Using logistic regression analysis in 741 patients with psoriasis and 1002 controls, the CARD 8 rs2043211 genotype was significantly different in cases and controls in overall terms [ OR 1.3 (1.1–1.5), P = 0.004] and for both genders. Our data support the hypothesis that the inflammasome plays a role in psoriasis susceptibility.